A
genome screen for risk factors in rheumatoid arthritis involving the largest
collection of US families to date yielded chromosome regions previously
implicated in the disease as well as regions implicated in other autoimmune
diseases, such as multiple sclerosis and inflammatory bowel disease. The
potential hotspots are regions of human chromosomes 1, 4, 12, 16, and
17.

Peter K. Gregersen, of North Shore University Hospital in Manhasset,
New York, led the multi-center study involving more than 250 families
recruited through the North American Rheumatoid Arthritis Consortium (NARAC).
The screens included 379 markers spaced throughout the human genome. Statistical
analyses using the markers and DNA from pairs of siblings were carried
out to determine chromosome regions that may contain genes of interest.

Structure of Families in the North American Rheumatoid
Arthritis Consortium (NARAC) Collection

Number of Families

Parents Available

Overall
(n = 257)

With Two Affected Sibs
(n = 231)

With Three Affected Sibs
(n = 240

With Four Affected Sibs
(n = 2)

Both

36

32

4

0

One

92

84

8

0

None

129

115a

12

2

a From one of these 115 families, five unaffected siblings
were available for analysis. Otherwise, information from unaffected
siblings was not used.Source: The American Journal of Human
Genetics

Published data connect rheumatoid arthritis to human leukocyte antigen
(HLA)-linked genes, which reside in a complex on chromosome 6. "This
study was undertaken specifically to identify genes outside of the HLA
region," the researchers write in a recent issue of The American
Journal of Human Genetics. "Given the increasing evidence for
familial aggregation and genetic overlap among different autoimmune diseases,
we also looked for evidence of common mapping results with other large
linkage-mapping studies of autoimmune diseases."

Five of the non-HLA regions reported in the study have been implicated
in at least one other autoimmune disease, including multiple sclerosis,
inflammatory bowel disease, systemic lupus erythematosus, and ankylosing
spondylitis.

The researchers conclude: "Genes in the HLA complex play a major
role in rheumatoid arthritis susceptibility, but several other regions
also contribute significantly to overall genetic risk."